The co-occurrence of mental health and substance use disorders (CMSD) has been identified as a major public health problem that imposes an enormous burden on individuals, families, and communities. The co- occurrence of alcohol use disorders (AUDs) and depression (C-ALDP) has received considerable attention because: (1) AUDs and depression are among the most prevalent psychiatric disorders. Recent epidemiologic studies indicated that the past 12-month prevalence rate of any AUD (including alcohol abuse and dependence) is about 8.5 percent of adults ages 18 and over (approximately 17.6 million adults), and the past 12- month prevalence rate of major depressive disorder (MDD) ranges between 5-6 percent of adults ages 18 and over (between 10 and 12 million adults). (2) AUDs and depression have relatively high rates of co-occurrence. About 40 percent of people with a lifetime depressive disorder also experience at least one AUD. (3) AUDs and depression are among the leading causes of disability in the world, as measured by disability-adjusted life years (DALYs) and years of life lived with disability (YLDs). Co-occurrence of AUDs and depression is associated with numerous negative outcomes, including greater risk for suicide. The available evidence indicates that AUDs, depression, and their co-occurrence emerge in adolescence with an increasing trajectory into young adulthood. Based on this evidence, the identification of the timing, temporal order, and developmental mechanisms for AUDs, depression, and their co-occurrence have been identified as high priority research questions. To address these questions, this project will conduct secondary analyses of the 2001-2002 and 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a prospective 3-year longitudinal study of a nationally representative sample of over 40,000 adults 18 and over. Using a developmental epidemiology framework, this project will address three specific aims: Aim 1: To examine the ages of onset (AO) of AUDs and depression as predictors of their co-occurrence. Aim 2: To examine alternative developmental models for co-occurring AUDs and MDD over a 3-year period. Aim 3: To examine the longitudinal course and clinical implications of co-occurring AUDs and MDD over a 3-year period. Results from this project will inform prevention and treatment efforts by identifying modifiable risk and protective factors for AUDs, depression, and their co-occurrence. This research will improve our understanding of the causes of three major public health problems: AUDs, depression, and their co- occurrence, and will increase knowledge related to preventing and treating these disorders. Results from this study have important implications for reducing the enormous burden of AUDs, depression, and their co- occurrence. 7. PROJECT NARRATIVE Alcohol use disorders, depression, and their co-occurrence are major public health problems that impose an enormous burden on individuals, families, and communities. This project will examine age and sex differences in the onset and course of alcohol use disorders and depression, and how they influence each other over time, in order to increase our knowledge related to preventing and treating these disorders.